TY - JOUR
T1 - Self-Interactions of Two Monoclonal Antibodies
T2 - Small-Angle X-ray Scattering, Light Scattering, and Coarse-Grained Modeling
AU - Mahapatra, Sujata
AU - Polimeni, Marco
AU - Gentiluomo, Lorenzo
AU - Roessner, Dierk
AU - Frieß, Wolfgang
AU - Peters, Günther H. J.
AU - Streicher, Werner W.
AU - Lund, Mikael
AU - Harris, Pernille
PY - 2022
Y1 - 2022
N2 - Using light scattering (LS), small-angle X-ray scattering (SAXS), and coarse-grained Monte Carlo (MC) simulations, we studied the self-interactions of two monoclonal antibodies (mAbs), PPI03 and PPI13. With LS measurements, we obtained the osmotic second virial coefficient, B22, and the molecular weight, Mw, of the two mAbs, while with SAXS measurements, we studied the mAbs' self-interaction behavior in the high protein concentration regime up to 125 g/L. Through SAXS-derived coarse-grained representations of the mAbs, we performed MC simulations with either a one-protein or a two-protein model to predict B22. By comparing simulation and experimental results, we validated our models and obtained insights into the mAbs' self-interaction properties, highlighting the role of both ion binding and charged patches on the mAb surfaces. Our models provide useful information about mAbs' self-interaction properties and can assist the screening of conditions driving to colloidal stability.
AB - Using light scattering (LS), small-angle X-ray scattering (SAXS), and coarse-grained Monte Carlo (MC) simulations, we studied the self-interactions of two monoclonal antibodies (mAbs), PPI03 and PPI13. With LS measurements, we obtained the osmotic second virial coefficient, B22, and the molecular weight, Mw, of the two mAbs, while with SAXS measurements, we studied the mAbs' self-interaction behavior in the high protein concentration regime up to 125 g/L. Through SAXS-derived coarse-grained representations of the mAbs, we performed MC simulations with either a one-protein or a two-protein model to predict B22. By comparing simulation and experimental results, we validated our models and obtained insights into the mAbs' self-interaction properties, highlighting the role of both ion binding and charged patches on the mAb surfaces. Our models provide useful information about mAbs' self-interaction properties and can assist the screening of conditions driving to colloidal stability.
KW - Monoclonal antibodies
KW - Light scattering
KW - Small-angle X-ray scattering
KW - Monte Carlo simulations
KW - Course-grained modeling
KW - Osmotic second virial coefficient
KW - Structure factor
KW - Colloidal stability
KW - Protein aggregation
U2 - 10.1021/acs.molpharmaceut.1c00627
DO - 10.1021/acs.molpharmaceut.1c00627
M3 - Journal article
C2 - 34939811
SN - 1543-8384
VL - 19
SP - 508
EP - 519
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
IS - 2
ER -